Langerhans cell (LC) proliferation mediates neonatal development, homeostasis, and inflammation-associated expansion of the epidermal LC network

Laurent Chorro, Aurélien Sarde, Mei Li, Kevin J. Woollard, Pierre Chambon, Bernard Malissen, Adrien Kissenpfennig, Jean Baptiste Barbaroux, Richard Groves, Frédéric Geissmann

Research output: Contribution to journalArticle

250 Scopus citations

Abstract

Most tissues develop from stem cells and precursors that undergo differentiation as their proliferative potential decreases. Mature differentiated cells rarely proliferate and are replaced at the end of their life by new cells derived from precursors. Langerhans cells (LCs) of the epidermis, although of myeloid origin, were shown to renew in tissues independently from the bone marrow, suggesting the existence of a dermal or epidermal progenitor. We investigated the mechanisms involved in LC development and homeostasis. We observed that a single wave of LC precursors was recruited in the epidermis of mice around embryonic day 18 and acquired a dendritic morphology, major histocompatibility complex II, CD11c, and langerin expression immediately after birth. Langerin+ cells then undergo a massive burst of proliferation between postnatal day 2 (P2) and P7, expanding their numbers by 10-20-fold. After the first week of life, we observed low-level proliferation of langerin+ cells within the epidermis. However, in a mouse model of atopic dermatitis (AD), a keratinocyte signal triggered increased epidermal LC proliferation. Similar findings were observed in epidermis from human patients with AD. Therefore, proliferation of differentiated resident cells represents an alternative pathway for development in the newborn, homeostasis, and expansion in adults of selected myeloid cell populations such as LCs. This mechanism may be relevant in locations where leukocyte trafficking is limited.

Original languageEnglish (US)
Pages (from-to)3089-3100
Number of pages12
JournalJournal of Experimental Medicine
Volume206
Issue number13
DOIs
StatePublished - Dec 21 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Chorro, L., Sarde, A., Li, M., Woollard, K. J., Chambon, P., Malissen, B., Kissenpfennig, A., Barbaroux, J. B., Groves, R., & Geissmann, F. (2009). Langerhans cell (LC) proliferation mediates neonatal development, homeostasis, and inflammation-associated expansion of the epidermal LC network. Journal of Experimental Medicine, 206(13), 3089-3100. https://doi.org/10.1084/jem.20091586